Insulin resistance and features of the metabolic syndrome are often associated with nonalcoholic fatty liver disease
Insulin resistance has been considered to be essential for the development of nonalcoholic fatty liver disease.
However, multiple mechanisms are involved in the pathogenesis of nonalcoholic fatty liver disease.
Dr Helma Cotrim and colleagues previously described a form of nonalcoholic fatty liver disease among petrochemical workers.
The investigators noted that predominantly younger men were affected, causing mild fibrosis and cholestasis.
In the current study the team evaluated the relationship of insulin resistance to nonalcoholic fatty liver disease among petrochemical workers.
| Most of the patients had no evidence of insulin resistance or metabolic risk factors|
|Journal of the American Medical Association|
The investigators included 40 petrochemical workers with the diagnosis of nonalcoholic fatty liver disease.
The participants presented with abnormal alanine aminotransferase, aspartate aminotransferase, and -glutamyltransferase levels on 3 or more determinations.
The patients were referred to the Hepatology Clinic, Federal University of Bahia, Brazil, between 2001 and 2003.
All had a history of occupational exposure to chemicals including benzene, xylene, ethylene, dimethylformamide, and vinyl chloride for at least 5 years.
Patients, corroborated by family members, indicated the absence of significant ethanol consumption.
The researchers excluded those with use of other drugs and presence of hepatitis B and C virus, hemochromatosis, and autoimmune diseases.
Insulin resistance was determined by the homeostasis model assessment (HOMA) index.
Control HOMA-insulin resistance values were obtained from 63 healthy volunteers.
The team considered insulin resistance to be present when the HOMA index value was 3 or higher.
The cut-off point was validated against the results of the quantitative insulin sensitivity check index.
The concordance between HOMA and quantitative insulin sensitivity check index was 100%.
The investigators found that insulin resistance was absent in 73% of the patients with nonalcoholic fatty liver disease.
Among the 11 patients with insulin resistance, all had hyperlipidemia, while 55% were obese, 73% were overweight, and 45% had diabetes.
The team noted that among 29 patients without insulin resistance, 35% had hyperlipidemia and 27% were also overweight, but without central obesity.
Hyperlipidemia, obesity, overweight, or diabetes were not observed in 38% of the patients.
Liver biopsy was performed on 80% of the patients.
The investigators detected steatohepatitis with fibrosis in 69% of these patients.
The investigative team also noted that 77% of the patients did not have insulin resistance.
All 5 patients with insulin resistance had steatohepatitis with fibrosis.
Dr Cotrim's team concluded, “To our knowledge, this is the first study to evaluate insulin resistance in patients with nonalcoholic fatty liver disease related to chemical exposure.”
“The majority of patients did not have evidence of insulin resistance or metabolic risk factors.”
“These results indicate that, contrary to prior assumptions, the development of fatty liver is not invariably associated with insulin resistance, and other mechanisms may be involved.”
“The absence of demonstrable insulin resistance may explain that this type of nonalcoholic fatty liver disease, usually asymptomatic, presents with mild histological findings that usually improve after workers are removed from exposure.”
“These findings suggest that the usual recommended measures for treating metabolic syndrome, such as diet and exercise, may have only limited efficacy in petrochemical-related nonalcoholic fatty liver disease.”
“However, the natural history of this form of nonalcoholic fatty liver disease and its relationship with co-existing metabolic syndrome deserves further investigation.”